1. Field of the Invention
The present invention relates to a process for producing optically active 3-aminobutanoic acid and ester intermediates which are produced in the above process. More particularly, the present invention relates to a process for producing optically active 3-aminobutanoic acids, which are useful for industrial fields, in the presence of a hydrolase, and new ester intermediates produced in the process.
2. Description of the Prior Art
Lately, it becomes important to synthesize physiologically active substances as optically active compounds. In a physiologically active substance having several kinds of optical isomers, these isomers often show difference in activity. Among these isomers, one isomer has strong activity and the other isomers show weak activity or undesired toxicity. Accordingly, when the physiologically active substances are synthesized as medical supplies, it is desired to selectively synthesize preferable optical isomers not only to develop full physiological activity but also in safety.
Optically active 3-amino butanoic acid is widely useful as intermediates for synthesizing physiologically active materials. For example, the above compound can be used as a starting material of peptide-like compounds having a function by which platelet aggregation is inhibited (R. B. Garland et al., EP 513810). Many production examples of optically active 3-aminobutanoic acid have been reported. For instance, as methods using asymmetric synthesis, 1) an asymmetric Michael method for adding an optically active lithium amide derivative to crotonic acid ester (S. G. Davies et al., Tetrahedron: Asymmetry, 2, 183 (1991)), and 2) a method for asymmetric reduction of 3-acylaminocrotonic acid ester with a BINAP-rhodium (II) complex (W. D. Lubell et al., Tetrahedron: Asymmetry, 2, 543 (1991) are known. As methods for using optical resolution, there are 3) a Michael method for adding optically active phenylethyl amine to crotonic acid ester to separate two obtained diastereomers by chromatography (E. Juaristi et al., J. Org. Chem., 57, 2396 (1992), and 4) a method of optical resolution by recrystalization of a diastereomer salt derived from racemic 3-aminobutanoic acid (M. Hunt et al., J. Biol. Chem., 127, 727 (1939), E. Fischer et al., Liebigs Ann. Chem., 383, 337 (1911)). As methods for using a biocatalyst, 5) a method of optical resolution of 3-acylaminobutanoic acid with benzylpenicillin acylase (D. Rossi et al., Experientia, 33, 1557 (1977) is known. Further, as a method for converting a commercially available optically active compound, which is used as a starting material, to optically active 3-aminobutanoic acid, there is 6) a method using L-aspartic acid (P. Gmeiner, Liebigs Ann. Chem., 1991, 501, C. W. Jefford et al., Tetrahedron Lett., 34, 1111 (1993)). However, method 1 ) needs a low temperature condition of -78.degree. C. Method 2) needs an expensive reagent and a special reaction equipment. Method 3) needs a chromatograph for separating isomers. Method 4) needs repeated recrystallization to obtain high optical purity. In method 5), it is difficult to obtain the enzyme. In method 6), there are many troublesome steps.
As described above, these conventional methods have problems of industrial level operation, unsatisfactorily. As an industrially useful method, there is an enzyme method. For example, a method for optical resolution of .alpha.-amino acid with a hydrolase, more particularly, a method for asymmetrically hydrolyzing an ester group to synthesize optically active .alpha.-amino acid is known. However, a method for synthesizing .beta.-amino acid (3-amino carboxylic acid) is quite unknown except a method reported by Zeebach (Helvetica Chimica Acta., 71, 1824 (1988)). The latter method has problems that both chemical and optical yield are very low (30% and 68%ee, respectively) and recrystallization should be repeated to enhance the optical purity.